Mechanisms of Severe Mortality-Associated Bacterial Co-infections Following Influenza Virus Infection.
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ABSTRACT:
SUBMITTER: Jia L
PROVIDER: S-EPMC5540941 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Peripheral blood was collected from human patients infected with influenza A virus only or in addition with bacterial pathogens and at different days after hospital admission. For comparison, blood from healthy controls was collected. Gene expression differences were detected in influenza and bacterial infections compared to healthy controls, and at various days post infection.
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Project description:Many questions remain concerning the burden, risk factors and impact of bacterial and viral co-infection in patients with pandemic influenza admitted to the intensive care unit (ICU).To examine the burden, risk factors and impact of bacterial and viral co-infection in Australian patients with severe influenza.A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples.Co-infection was identified in 23·3-26·9% of patients with severe influenza A infection: viral co-infection, 3·2-3·4% and bacterial co-infection, 20·5-24·7%. Staphylococcus aureus was the most frequent bacterial co-infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co-infection were younger [mean difference in age = 8·46 years (95% CI: 0·18-16·74 years)], less likely to have significant co-morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77-11·96)] compared to those without co-infection.?Bacterial or viral co-infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co-infected patients being younger and with fewer co-morbidities, no significant difference in outcomes was observed. It is likely that co-infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease. Empiric antibiotics with staphylococcal activity should be strongly considered in all patients with severe influenza A infection.
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Project description:Influenza associated bacterial super-infections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory prior to adulthood. Due to this we sought to understand the role of immune memory during bacterial super-infections. An influenza heterotypic immunity model was established using influenza A/PR/8/34 and A/X31. We report here that influenza experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naïve animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer specific CD8+ T cells. The protection that was seen in memory experienced mouse model is associated with the reduction in inflammatory mechanisms making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity re-shapes the lung environment and the immune response to a re-challenge event, which is highly relevant to the context of human infection.
2022-06-27 | GSE206095 | GEO
Project description:Methicillin-resistant Staphylococcus aureus has emerged as a significant contributor to morbidity and mortality associated with influenza infection. In this study, we show in a mouse model that preceding influenza infection promotes S. aureus resistance to killing by antibiotics. This resistance coincides with influenza-induced accumulation of inflammatory monocytes in the lung. CCR type 2 (CCR2) is responsible for pulmonary monocyte recruitment after influenza infection. We found that antibiotic-treated Ccr2-deficient (Ccr2-/-) mice exhibit significantly improved bacterial control and survival from influenza and methicillin-resistant S. aureus coinfection, despite a delay in viral clearance. Mechanistically, our results from in vivo studies indicate that influenza-induced monocytes serve as reservoirs for intracellular S. aureus survival, thereby promoting bacterial resistance to antibiotic treatment. Blocking CCR2 with a small molecular inhibitor (PF-04178903), in conjunction with antibiotic treatment, enhanced lung bacterial clearance and significantly improved animal survival. Collectively, our study demonstrates that inflammatory monocytes constitute an important and hitherto underappreciated mechanism of the conflicting immune requirements for viral and bacterial clearance by hosts, which subsequently leads to exacerbated outcomes of influenza and S. aureus coinfection.
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Project description:BackgroundA mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP).MethodsA retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics.ResultsCompared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)].ConclusionsThe prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.
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Project description:PurposeWhile most influenza patients have a self-limited respiratory illness, 5-10% of hospitalized patients develop severe disease requiring ICU admission. The aim of this study was to identify influenza-specific factors associated with ICU admission and mortality. Furthermore, influenza-specific pulmonary bacterial, fungal and viral co-infections were investigated.Methods199 influenza patients, admitted to two academic hospitals in the Netherlands between 01-10-2015 and 01-04-2016 were investigated of which 45/199 were admitted to the ICU.ResultsA history of Obstructive/Central Sleep Apnea Syndrome, myocardial infarction, dyspnea, influenza type A, BMI?>?30, the development of renal failure and bacterial and fungal co-infections, were observed more frequently in patients who were admitted to the ICU, compared with patients at the normal ward. Co-infections were evident in 55.6% of ICU-admitted patients, compared with 20.1% of patients at the normal ward, mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, and Aspergillus fumigatus. Non-survivors suffered from diabetes mellitus and (pre-existent) renal failure more often.ConclusionsThe current study indicates that a history of OSAS/CSAS, myocardial infarction and BMI?>?30 might be related to ICU admission in influenza patients. Second, ICU patients develop more pulmonary co-infections. Last, (pre-existent) renal failure and diabetes mellitus are more often observed in non-survivors.
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